Objective: Adipose-derived mesenchymal stem cells (ADSCs) offer great promise as cell therapy for ischaemic diseases. Due to their poor survival in the ischaemic environment, the therapeutic efficacy of ADSCs is still relatively low. Interleukin-11 (IL-11) has been shown to play a key role in promoting cell proliferation and protecting cells from oxidative stress injury. The aim of this study was to determine whether IL-11 could improve therapeutic efficacy of ADSCs in ischaemic diseases.
Methods and results: ADSCs were prepared from inguinal subcutaneous adipose tissue and exposed to hypoxic environment. The protein expression of IL-11 was decreased after hypoxic treatment. In addition, ADSCs viability was increased after IL-11 treatment under hypoxia. Moreover, IL-11 enhanced ADSCs viability in a dose-dependent manner under normoxia. Importantly, IL-11 promoted ADSCs proliferation and migration and protected ADSCs against hydrogen peroxide-induced cellular death. Notably, IL-11 enhanced ADSCs proliferation and migration, also promoted cell survival and apoptosis resistance by STAT3 signalling. In vivo, mice were subjected to limb ischaemia and treated with IL-11 overexpression ADSCs and control ADSCs. IL-11 overexpression ADSCs improved perfusion recovery in the ischaemic muscles.
Conclusions: We provide the evidence that IL-11 promoted ADSCs proliferation, stimulated ADSCs migration and attenuated ADSCs apoptosis by activation of STAT3 signalling. These results suggest that IL-11 facilitated ADSCs engraftment in ischaemic tissue, thereby enhanced ADSCs therapeutic efficacy.
Keywords: adipose-derived mesenchymal stem cells; cell therapy; interleukin-11; limb ischaemia.
© 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.